Synthesis of N4-(2,4-dimethylphenyl) semicarbazones as 4-aminobutyrate aminotransferase inhibitors

Acta Pharm. 2006 Sep;56(3):259-72.

Abstract

Several 2,4-dimethylphenyl substituted semicarbazones were synthesized in three steps involving aryl urea and aryl semicarbazide formation. The structures were confirmed by spectral and elemental analyses. All the compounds were evaluated for anticonvulsant activity by using a series of test models, including maximal electroshock seizure, subcutaneous pentylenetetrazole and subcutaneous strychnine seizure threshold tests. The compounds were also evaluated for behavioural impairement and depression activity. In the neurochemical investigation, potent compounds were evaluated for their effects on rat brain gamma-aminobutyric acid (GABA) levels and in vitro gamma-aminobutyrate transaminase (Pseudomonas fluorescens) activity. Preliminary studies suggest that these compounds exhibit anticonvulsant activity via a GABA-mediated mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Aminobutyrate Transaminase / antagonists & inhibitors*
  • Animals
  • Anticonvulsants / chemical synthesis
  • Anticonvulsants / pharmacology*
  • Behavior, Animal / drug effects
  • Brain / metabolism
  • Disease Models, Animal
  • Male
  • Mice
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Wistar
  • Seizures / drug therapy*
  • Semicarbazones / chemical synthesis
  • Semicarbazones / pharmacology*
  • gamma-Aminobutyric Acid / drug effects
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Anticonvulsants
  • Semicarbazones
  • gamma-Aminobutyric Acid
  • 4-Aminobutyrate Transaminase